In order to identify a substance with a large molecular weight and analyze its structure, one of known techniques of mass spectrometry is MS/MS analysis (also called tandem analysis). A typical MS/MS mass spectrometer is a triple quadrupole mass spectrometer having quadrupole mass filters arranged upstream and downstream of a collision cell that dissociates an ion.
In general MS/MS analysis, first, a target ion species having a specific mass-to-charge ratio (mass m/valence z) is sorted out as a precursor ion from among ion species generated from a sample containing a substance to be analyzed, and the sorted-out precursor ion is dissociated through collision induced dissociation (CID) method, electron capture dissociation (ECD) method or the like to generate product ions. This is selection and dissociation operation of an ion species. Then, similarly to normal mass spectrometry, various product ions thus generated are separated and detected according to mass-to-charge ratios. Since an ion species originated from a certain kind of substance causes a characteristic form of dissociation through CID or ECD, for example, detecting a site of occurrence of the dissociation can lead to a conclusion that the substance to be analyzed has a specific chemical structure.
In the aforementioned triple quadrupole mass spectrometer, the selection operation of the precursor ion is performed in a front-stage quadrupole mass filter; in a subsequent collision cell, the dissociation operation of the precursor ion is performed; and in a further subsequent rear-stage quadrupole mass filter, mass separation of the product ions is performed. Typically, the mass-to-charge ratio of the ion selected through the front-stage quadrupole mass filter and the mass-to-charge ratio of the ion selected through the rear-stage quadrupole mass filter can be independently and freely set.
Three well-known scanning measurement techniques in the MS/MS analysis are product ion scanning, precursor ion scanning and neutral loss scanning (for example, see Patent Literature 1). In the product ion scanning, all the product ions that are generated from a specific precursor ion are scanned to create a so-called mass spectrum. In the precursor ion scanning, conversely, all the precursor ions that generate a specific product ion are scanned. Moreover, in the neutral loss scanning, all the precursor ions that a specific partial structure is eliminated are searched for by scanning the mass-to-charge ratios of the ions that can pass through both mass filters such that a difference between the mass-to-charge ratios of the ions passing through the front-stage and rear-stage quadrupole mass filters is constant.
The feature of the latter two techniques is that only the precursor ion having a certain specific product ion or neutral loss is specifically detected. Typically, when a fragment eliminated from the precursor ion through the dissociation operation does not have a charge (is neutral), the neutral loss scanning is used, and when the fragment has a charge, the precursor ion scanning is used.
The neutral loss scanning is an analysis technique that makes it possible to detect an ion pair having a mass-to-charge ratio difference, between the precursor ion and the product ion, that is specific to a structure such as a functional group, and is particularly useful in the case where a protein is class-specifically identified or the similar case. However, in neutral loss scanning in a conventional MS/MS mass spectrometer, it is assumed that the eliminated fragment is neutral. Therefore, in the case where the valence of the product ion is different from the valence of the precursor ion due to, for example, a charged fragment being eliminated by dissociating a multivalent precursor ion through CID, neutral loss scanning cannot be performed. Moreover, in a dissociation through ECD, although the eliminated fragment is neutral, the valence of the product ion differs from the valence of the precursor ion through the dissociation. Therefore, the mass-to-charge ratio difference between the two ions is not constant, and neutral loss scanning cannot be applied either.
Moreover, when a multivalent precursor ion is dissociated through CID and a charged fragment is eliminated, both of the eliminated fragment and the product ion after elimination have charges. This means that not only the product ion but also the eliminated fragment can be detected when the ion originated from the sample is a multivalent ion. In general, in the quadrupole mass filter and a multipole ion guide implemented in the collision cell, the range of mass-to-charge ratios of ions that can stably pass through is limited to a certain extent, and therefore, when the mass-to-charge ratio of the product ion to be detected is too small or too large, such a product ion cannot adequately pass through the collision cell or the rear-stage quadrupole mass filter, which deteriorates detection sensitivity. If the mass-to-charge ratio of an ion generated through dissociation of a multivalent ion can be arbitrarily selected and stably detected, by selectively detecting either one of the product ion generated from the ion originated from a certain component and the eliminated charged fragment, useful information regarding the component can be obtained at high sensitivity. However, an MS/MS mass spectrometer that can perform such analysis on the multivalent ion does not conventionally exist.
Moreover, when a compound containing an element having a characteristic isotope pattern, such as chlorine, is analyzed, if the mass-to-charge ratio of an ion generated through dissociation of a multivalent ion originated from the compound can be arbitrarily selected and detected, information of the position of the element in the compound may be obtained by confirming whether or not the aforementioned isotope pattern exists in the detected ion. However, an MS/MS mass spectrometer that can perform such analysis on the multivalent ion does not conventionally exist.